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Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters

Author

Listed:
  • Changxu Pang

    (Brookhaven National Laboratory)

  • Jin Chai

    (Brookhaven National Laboratory)

  • Ping Zhu

    (Brookhaven National Laboratory)

  • John Shanklin

    (Brookhaven National Laboratory)

  • Qun Liu

    (Brookhaven National Laboratory
    Brookhaven National Laboratory)

Abstract

Zinc is an essential micronutrient that supports all living organisms through regulating numerous biological processes. However, the mechanism of uptake regulation by intracellular Zn2+ status remains unclear. Here we report a cryo-electron microscopy structure of a ZIP-family transporter from Bordetella bronchiseptica at 3.05 Å resolution in an inward-facing, inhibited conformation. The transporter forms a homodimer, each protomer containing nine transmembrane helices and three metal ions. Two metal ions form a binuclear pore structure, and the third ion is located at an egress site facing the cytoplasm. The egress site is covered by a loop, and two histidine residues on the loop interact with the egress-site ion and regulate its release. Cell-based Zn2+ uptake and cell growth viability assays reveal a negative regulation of Zn2+ uptake through sensing intracellular Zn2+ status using a built-in sensor. These structural and biochemical analyses provide mechanistic insight into the autoregulation of zinc uptake across membranes.

Suggested Citation

  • Changxu Pang & Jin Chai & Ping Zhu & John Shanklin & Qun Liu, 2023. "Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39010-6
    DOI: 10.1038/s41467-023-39010-6
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    1. Lan Zhao & Eduardo Oliver & Klio Maratou & Santosh S. Atanur & Olivier D. Dubois & Emanuele Cotroneo & Chien-Nien Chen & Lei Wang & Cristina Arce & Pauline L. Chabosseau & Joan Ponsa-Cobas & Maria G. , 2015. "The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia," Nature, Nature, vol. 524(7565), pages 356-360, August.
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